The primary objective of this research is to continue to develop new strategies of the construction of complex carbocyclic or heterocyclic ring systems. It is expected that this new methodology will expedite the syntheses of biologically active natural products and /or analogs as well as de novo bioactive compounds. Analogs of the promising anticancer agent taxol will be prepared via two complementary Claisen-rearrangement-based strategies for taxane synthesis. Each of these approaches involves successive ring annelations (CyieldsCByieldsCBA and AyieldsAByieldsABC) and features a stereocontrolled cyclooctane annexation. The taxane ring system will also be constructed ba route which exploits a titanium-promoted eight- membered ring closure reaction. These new taxane derivatives will feature highly variable substitution patterns along the lower periphery of the molecule and will further elucidate which functional groups are required for biological activity. Hopefully, a simplified, biologically active analog of taxol will be discovered. The first total synthesis of ingenol will be complected. More importantly, the tumor promoter analogs, 4.5-dideoxyingenol-3 tetradecanoate and 5-deoxyingenol-3-tetradecanoate will also be prepared. These analogs will permit the several conflicting tumor promoter pharmacophore hypotheses to be rigorously tested. Delineation of the tumor promoter pharmacophore could facilitate the development of new signal transduction-based chemotherapeutic agents. A new class of DNA photocleaving agents will be developed by exploiting recently discovered photochemical Bergman reactions of ortho- dialkynylarenes. These new DNA photocleaving agents are novel in that the binding and photoactive domains are consolidated and , moreover, generate two reactive sites for subsequent ribose hydrogen atom abstraction(s). attachment of these DNA photocleaving agents to DNA recognition domains such as antisense oligonucleotides or protein scaffolds could result in novel anticancer and/or antiviral photo- therapeutic agents and new tools for biotechnology (photonucleases or protein footprinting). Finally, the carbon-carbon bond forming potential of the Bergman cyclization reaction will be examined in the context of a natural products synthesis, specifically, lysergic acid.